Papers by Jonathan Coulter
Imaging intracellular and systemic in vivo gold nanoparticles to enhance radiotherapy
The British journal of radiology, Jan 29, 2015
Nanoparticles offer alternative options in cancer therapy both as drug delivery carriers and as d... more Nanoparticles offer alternative options in cancer therapy both as drug delivery carriers and as direct therapeutic agents for cancer cell inactivation. More recently gold nanoparticles (AuNPs) have emerged as promising radio-sensitizers achieving significantly elevated radiation dose enhancement factors when irradiated with both keV and MeV X-rays. Use of AuNPs in radiobiology is now being intensely driven by the desire to achieve precise energy deposition in tumors. As a consequence, there is a growing demand for efficient and simple techniques for detection, imaging and characterization of AuNPs in both biological and tumor samples. Spatially accurate imaging on the nano-scale poses a serious challenge requiring high or super resolution imaging techniques. In this mini review, we discuss the challenges in using AuNPs as radiosensitisers as well as various current and novel imaging techniques designed to validate the uptake, distribution and localization in mammalian cells. In our ...
Oncotarget, Jan 19, 2015
Metastasis is the predominant cause of death from cancer yet we have few biomarkers to predict pa... more Metastasis is the predominant cause of death from cancer yet we have few biomarkers to predict patients at increased risk of metastasis and are unable to effectively treat disseminated disease. Analysis of 448 primary breast tumors determined that expression of the hylauronan receptor CD44 associated with high grade (p = 0.046), ER- (p = 0.001) and PR-negative tumors (p = 0.029), and correlated with increased distant recurrence and reduced disease-free survival in patients with lymph-node positive or large tumors. To determine its functional role in distant metastasis, CD44 was knocked-down in MDA-MB-231 cells using two independent shRNA sequences. Loss of CD44 attenuated tumor cell adhesion to endothelial cells and reduced cell invasion but did not affect proliferation in vitro. To verify the importance of CD44 to post-intravasation events, tumor formation was assessed by quantitative in vivo imaging and post-mortem tissue analysis following an intra-cardiac injection of transfecte...
A20. Inductible nitric oxide synthase gene therapy for cancer
The development of a novel biomimetic vector for targeted cancer gene therapy
Development of a novel PSMA-driven gene therapy strategy for the treatment of prostate cancer
hOC/iNOS-A novel gene therapy approach for the treatment of advanced hormone refractory prostate cancer
Enhancement of the anti-cancer potential of iNOS gene therapy under the control of a radiation-responsive synthetic CArG promoter
TARGETING NITROSATIVE STRESS FOR CANCER THERAPY
Drug Discovery Today • Volume 15, Numbers 23/24 • December 2010 colocalization degree over time. ... more Drug Discovery Today • Volume 15, Numbers 23/24 • December 2010 colocalization degree over time. Additionally the internalization kinetics of integrin targeted micelles was compared to EGF targeted polyplexes that are well-known for their fast uptake kinetics [2]. The internalization pathway was then studied with inhibitor experiments and by colocalization with specific marker proteins. Our results reveal a strong competition between unspecific electrostatic interactions and specific receptor-ligand interactions that determines successful targeting of the micelles. Enhanced PEG shielding of the micelles leads to the reduction of electrostatic interactions resulting in a specific and faster internalization of the targeted micelles. Additionally we observed a considerable effect of the applied micelle concentration as well as the micelle size on their internalization properties. Our data lead to a more detailed understanding of the targeting effect than can be observed by conventional bulk instruments. The gained knowledge enables to maximize the therapeutic benefit of future gene vectors for clinical application. Reference 1. Oba M, et al. Cyclic RGD peptide-conjugated polyplex micelles as a targetable gene delivery system directed to cells possessing alphav-beta3 and alphavbeta5 integrins. Bioconjug Chem 2007;18:1415-23. 2. de Bruin K, et al. Cellular dynamics of EGF receptor-targeted synthetic viruses. (H.O. McCarthy).
All that is gold does not glitter, not all those that wander are lost': the dual behaviour of gold nanoparticles in vitro
Sensitivity of PTEN-deficient prostate carcinoma cells to ionizing radiation through inhibition of treatment-induced CXCL8 signaling
Assessment of a novel peptide-based gene therapy vehicle for hOC/iNOS targeting of metastatic prostate and breast cancer
Abstract C215: Sensitivity of PTEN-deficient prostate carcinoma xenografts to ionizing radiation through inhibition of treatment-induced CXCL8 signaling
Oral 1922-3-Nitric oxide synthase gene therapy: A potent therapeutic in metastatic breast cancer
Bio-inspired Vectors for Gene Therapy
Background Gene therapy has been identified as a promising treatment strategy for hormone refract... more Background Gene therapy has been identified as a promising treatment strategy for hormone refractory prostate cancer (HRPC). We report, for the first time, the use of the human osteocalcin (hOC) promoter to control inducible nitric oxide synthase (iNOS) transgene expression in HRPC.
Scientific reports, 2011
Gold nanoparticles (GNPs) are being proposed as contrast agents to enhance X-ray imaging and radi... more Gold nanoparticles (GNPs) are being proposed as contrast agents to enhance X-ray imaging and radiotherapy, seeking to take advantage of the increased X-ray absorption of gold compared to soft tissue. However, there is a great discrepancy between physically predicted increases in X-ray energy deposition and experimentally observed increases in cell killing. In this work, we present the first calculations which take into account the structure of energy deposition in the nanoscale vicinity of GNPs and relate this to biological outcomes, and show for the first time good agreement with experimentally observed cell killing by the combination of X-rays and GNPs. These results are not only relevant to radiotherapy, but also have implications for applications of heavy atom nanoparticles in biological settings or where human exposure is possible because the localised energy deposition high-lighted by these results may cause complex DNA damage, leading to mutation and carcinogenesis.
International journal of nanomedicine, 2012
This follow-up study aims to determine the physical parameters which govern the differential radi... more This follow-up study aims to determine the physical parameters which govern the differential radiosensitization capacity of two tumor cell lines and one immortalized normal cell line to 1.9 nm gold nanoparticles. In addition to comparing the uptake potential, localization, and cytotoxicity of 1.9 nm gold nanoparticles, the current study also draws on comparisons between nanoparticle size and total nanoparticle uptake based on previously published data. We quantified gold nanoparticle uptake using atomic emission spectroscopy and imaged intracellular localization by transmission electron microscopy. Cell growth delay and clonogenic assays were used to determine cytotoxicity and radiosensitization potential, respectively. Mechanistic data were obtained by Western blot, flow cytometry, and assays for reactive oxygen species. Gold nanoparticle uptake was preferentially observed in tumor cells, resulting in an increased expression of cleaved caspase proteins and an accumulation of cells ...
Nitric oxide synthase gene therapy: A potent therapeutic in metastatic breast cancer
Nitric Oxide, 2014
The Journal of Physical Chemistry C, 2011
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Papers by Jonathan Coulter